Stroke is among the leading causes of death and disability in adults in the U.S. Over the past several decades, clinical studies have identified many environmental risk factors for stroke such as hypertension, diabetes mellitus and cigarette smoking. More recent evidence suggests that genetic components also contribute to the risk of stroke as well. Growth in the understanding of the human genome and advances in genetic epidemiology, make it possible to clarify the genetic contributions to complex diseases such as ischemic stroke. The overall long-term objective of this application is to search for regions of interest in the human genome that may harbor stroke susceptibility genes. The primary aim of the application is to collect DNA samples from 300 sibling pairs concordant for ischemic stroke and to perform a genome wide screen for genetic risk factors for ischemic stroke in these individuals. The screen will employ microsatellite markers spaced at a maximum of 20 centamorgan intervals. Secondary aims include: (1) identifying genetic regions of interest associated with ischemic stroke in adults below age 50 years and (2) identifying genetic regions of interest that are independent of stroke risk factors such as diabetes, hypertension, cigarette smoking, and atrial fibrillation. Probands will be screened for sibs concordant for stroke from patients with acute ischemic stroke who present to hospitals that are participating in the NIH-sponsored trial comparing carotid angioplasty/stenting to endarterectomy (CREST RO1-NS38384-01). A centralized stroke verification committee will assure and accuracy in stroke phenotyping. DNA banking will be done to permitted future collaborative efforts to study the genetic basis for stroke risk.